Giovanni Pavesi

Corticospinal excitability is specifically modulated by motor imagery : a magnetic stimulation study

Transcranial magnetic stimulation (TMS) was used to investigate whether the excitability of the corticospinal system is selectively affected by motor imagery. To this purpose, we performed two experiments. In the first one we recorded motor evoked potentials from right hand and arm muscles during mental simulation of flexion/extension movements of both distal and proximal joints. In the second experiment we applied magnetic stimulation to the right and the left motor cortex of subjects while they were imagining opening or closing their right or their left hand. Motor evoked potentials (MEPs) were recorded from a hand muscle contralateral to the stimulated cortex. The results demonstrated that the excitability pattern during motor imagery dynamically mimics that occurring during movement execution. In addition, while magnetic stimulation of the left motor cortex revealed increased corticospinal excitability when subjects imagined ipsilateral as well as contralateral hand movements, the stimulation of the right motor cortex revealed a facilitatory effect induced by imagery of contralateral hand movements only. In conclusion, motor imagery is a high level process, which, however, manifests itself in the activation of those same cortical circuits that are normally involved in movement execution.

Peripheral neuropathy in Wegener’s granulomatosis, Churg–Strauss syndrome and microscopic polyangiitis

Objective: To compare the clinical aspects of peripheral neuropathy associated with Wegener’s granulomatosis (WG), Churg–Strauss syndrome (CSS) and microscopic polyangiitis (MP). Methods: Cohort study conducted in a single university hospital. Patients were included when a definite diagnosis of WG, CSS or MP was made according to the current classification criteria in our hospital, between 1999 and 2006. All patients underwent periodically clinical and electrophysiological screening for peripheral neuropathy, assessment of disability, and clinical and laboratory evaluation during a mean follow-up of 38 months. Results: Sixty-four consecutive patients diagnosed with WG (26 patients), CSS (26 patients) and MP (12 patients) were recruited. Peripheral neuropathy occurred in 27/64 patients: six with WG, 15 with CSS and six with MP. Neuropathy occurred earlier in the disease history in CSS and MP compared with WG. Among patients with WG, those who developed peripheral neuropathy during follow-up were older than those without neuropathy both at the time of onset and of diagnosis of vasculitis. Distal symmetric polyneuropathy was present in 11 patients, and single or multiple mononeuropathy in 16. Patients with WG had a less severe form of mononeuritis multiplex than CSS or MPA patients. Disability and pain were greater in patients with mononeuropathy, although one-third of them were painless. Relapses of neuropathy were extremely infrequent. Conclusions: Peripheral neuropathy in WG occurs less frequently, later in the disease course and in a milder form than in CSS and MP. Single or multiple mononeuropathy associated with these subsets of vasculitis can often be painless.

Cryoglobulinaemic neuropathy manifesting with restless legs syndrome

In a series of 12 patients with essential mixed cryoglobulinaemia (EMC) and peripheral neuropathy as main feature of the disease, restless legs syndrome (RLS) was a major manifestation in four women, aged 55-65 years. In one patient RLS was a presenting manifestation of the disease, and in another patient the diagnosis of EMC was made investigating RLS and polyneuropathy, although prior rheumatological symptoms were retrospectively recognized. All patients with RLS had symmetrical sensory polyneuropathy, but non-RLS patients had also other forms of peripheral neuropathy, and symmetrical sensory polyneuropathy only in two of eight cases (P=0.03). Neurophysiological study showed that sensory action potentials of the sural nerve were more often inelicitable in non-RLS patients (six of eight) than in RLS patients (none of three). Sural nerve biopsy had no distinctive features in three RLS patients, with regard to other patients with cryoglobulinaemic neuropathy. RLS seems not uncommon in cryoglobulinaemic neuropathy, and significantly associated with symmetrical sensory polyneuropathy, whereas patients with other subtypes of cryoglobulinaemic neuropathy do not develop RLS; thus, a disorder of the sensory inputs may be important in the pathogenesis of RLS. The occurrence of RLS, especially in middle-aged women, should prompt investigations for peripheral neuropathy focusing on cryoglobulinaemic neuropathy.

Peripheral neuropathy in essential mixed cryoglobulinaemia.

The prevalence of various forms of peripheral neuropathy has not been previously assessed in large series of patients with essential mixed cryoglobulinaemia (EMC). Clinical and electrophysiological signs of peripheral neuropathy were observed in 21 of 37 EMC patients, consisting of polyneuropathy in 19, mononeuropathy or multiple mononeuropathy in eight, and both in six. The various forms of peripheral neuropathy occurred differently in the subgroups of EMC. Isolated polyneuropathy was more common with type II (eight of 10) than type III EMC (two of eight). Multifocal neuropathy, in association with polyneuropathy, was the most common form in type III EMC (five of eight). Patients with peripheral neuropathy and type II EMC were significantly older than type II EMC patients without neuropathy, regarding present age and age of onset of EMC. Patients with peripheral neuropathy and type III EMC tended to have higher values of ESR and IgM than type III EMC patients without neuropathy. Electrophysiological findings and sural nerve biopsy specimens (nine cases) showed prominent axonal changes. Vascular changes included vasculitis and alterations of the endoneurial microvessels in type II and type III EMC. Our findings suggest that distinct pathogenic factors are implicated in the subgroups of cryoglobulinaemic neuropathy, possibly inducing different types of vascular changes underlying polyneuropathy or, respectively, mononeuropathy and multiple mononeuropathy.

Impairment of corneal pain perception in cluster headache

&NA; Despite many studies, the mechanisms underlying the pathogenesis of pain in cluster headache (CH) still remain obscure. An involvement of substance P (SP) containing neurons of the Gasserian ganglion and/or of the spinal trigeminal nucleus has recently been suggested, e.g., by impairment of inhibitory descending pathways on trigeminal nociceptive neurons. The electrically elicited corneal reflex was studied in 21 CH patients (15 in active phase, 6 in remission). This method allows simultaneous measurements of the trigemino‐facial reflex and corneal pain perception. A significant reduction of pain thresholds (more evident on the pain side) was observed in CH during the active phase, while normal values were recorded during the remission phase. Ten out of 15 patients in the active phase showed a significantly reduced corneal pain threshold on the pain side, while tactile sensibility was normal. Moreover, latency, amplitude and duration of the corneal reflex were normal for both painful and painless stimulations during both phases. The threshold of the nociceptive muscular response in the active phase was significantly reduced, suggesting that the excitability of trigeminal nociceptive neurons or of the motor neurons is increased in CH. The results agree with the hypothesis that a reversible impairment of several integrative functions, including the activity of trigeminal pain control system, exists in CH during the active phase.

The facial motor system

Facial movements support a variety of functions in human behavior. They participate in automatic somatic and visceral motor programs, they are essential in producing communicative displays of affective states and they are also subject to voluntary control. The multiplicity of functions of facial muscles, compared to limb muscles, is reflected in the heterogeneity of their anatomical and histological characteristics that goes well beyond the conventional classification in single facial muscles. Such parcellation in different functional muscular units is maintained throughout the central representation of facial movements from the brainstem up to the neocortex. Facial movements peculiarly lack a conventional proprioceptive feedback system, which is only in part vicariated by cutaneous or auditory afferents. Facial motor activity is the main marker of endogenous affective states and of the affective valence of external stimuli. At the cortical level, a complex network of specialized motor areas supports voluntary facial movements and, differently from upper limb movements, in such network there does not seem to be a prime actor in the primary motor cortex.

Acute sensory and autonomic neuropathy: possible association with coxsackie B virus infection.

This report describes a 26 year old woman with a Coxsackie B virus infection complicated by an acute pandysautonomic and sensory neuropathy. Electrophysiological studies suggested an axonal neuropathy. A sural nerve biopsy performed early in the disease showed axonal degeneration with a virtual absence of unmyelinated fibres and moderate loss of myelinated fibres, mainly affecting the small fibres; this differs from previous reports. An immune-mediated or direct virus action might explain the pathogenesis of this unusual evolution of a viral infection.

The localization of facial motor impairment in sporadic Möbius syndrome

Objective: To investigate the neurophysiologic aspects of facial motor control in patients with sporadic Möbius syndrome defined as nonprogressive congenital facial and abducens palsy. Methods: The authors assessed 24 patients with sporadic Möbius syndrome by performing a complete clinical examination and neurophysiologic tests including facial nerve conduction studies, needle electromyography examination of facial muscles, and recording of the blink reflex and of the trigeminofacial inhibitory reflex. Results: Two distinct groups of patients were identified according to neurophysiologic testing. The first group was characterized by increased facial distal motor latencies (DMLs) and poor recruitment of small and polyphasic motor unit action potentials (MUAPs). The second group was characterized by normal facial DMLs and neuropathic MUAPs. It is hypothesized that in the first group, the disorder is due to a rhombencephalic maldevelopment with selective sparing of small-size MUs, and in the second group, the disorder is related to an acquired nervous injury during intrauterine life, with subsequent neurogenic remodeling of MUs. The trigeminofacial reflexes showed that in most subjects of both groups, the functional impairment of facial movements was caused by a nuclear or peripheral site of lesion, with little evidence of brainstem interneuronal involvement. Conclusion: Two different neurophysiologically defined phenotypes can be distinguished in sporadic Möbius syndrome, with different pathogenetic implications.

Pathological yawning as a presenting symptom of brain stem ischaemia in two patients

Two cases of brain stem stroke involving the upper pons and the ponto-mesencephalic junction presented with transient excessive pathological yawning, associated with gait ataxia and in one subject with upper limb and facial hemiparesis. A causal relation is hypothesised between the brain stem lesion and pathological yawning, possibly related to denervation hypersensitivity of a putative brain stem yawn centre. Excessive yawning may herald brain stem ischaemia.

Masseteric repetitive nerve stimulation in the diagnosis of myasthenia gravis

OBJECTIVE (1) to develop a method for masseteric repetitive nerve stimulation (RNS) and to obtain normative data for amplitude and area decrement of the muscle (M) response. (2) To investigate myasthenia gravis (MG) patients with masseteric RNS. Masticatory muscles are frequently affected in MG, but no RNS test is available to investigate this district. METHODS Fifteen healthy subjects and 17 MG patients were examined. The masseteric nerve was stimulated by a monopolar needle (cathode), inserted between the mandibular incisure and the zygomatic arch, and a surface electrode (anode), on the contralateral cheek. Masseteric M response was recorded using surface electrodes on the muscle belly and below the mandibular angle. Stimuli were delivered at 3 Hz in trains of 9, at rest and after isometric effort. RESULTS Normal subjects: mean amplitude decrement was 0.3+/-1.2% at rest, and 1.9+/-1.3% after isometric effort. PATIENTS 15 patients (88%) were positive on masseteric RNS; in 3 of these it was the only positive RNS test. The extent of decrement observed in masseter muscle was significantly greater than in trapezius muscle. CONCLUSIONS Masseteric RNS is a simple and well-tolerated procedure; it offers a new possibility in testing the cranial muscles in disorders of neuromuscular transmission.